3,4-Methylenedioxymethamphetamine (MDMA - Ecstasy) Decreases Neutrophil Activity Through the Glucocorticoid Pathway and Impairs Host Resistance to Listeria Monocytogenes Infection in Mice

Autor(es)

Ferraz-de-Paula, V. ^[1] ; Ribeiro, A. ^[1] ; Souza-Queiroz, J. ^[2] ; Pinheiro, M. L. ^[1] ; Vecina, J. F. ^[2] ; Souza, D. P. M. ^[3] ; Quinteiro-Filho, W. M. ^[1] ; Moreau, R. L. M. ^[4] ; Queiroz, M. L. S. ^[2] ; Palermo-Neto, J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Vet Med, Dept Pathol, Neuroimmunomodulat Res Grp, BR-05508270 Sao Paulo - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Fac Med Sci, Dept Pharmacol, Ctr Hematol & Hemotherapy, Campinas, SP - Brazil

^[3] Fed Univ Tocantins, Sch Vet Med & Anim Sci, Trop & Anim Sci Program, Tocantins - Brazil

^[4] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508270 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NEUROIMMUNE PHARMACOLOGY; v. 9, n. 5, p. 690-702, DEC 2014.
• Citações Web of Science: 6

Resumo

Ecstasy is the popular name of the abuse drug 3,4-methylenedioxymethamphetamine (MDMA) that decreases immunity in animals. The mechanisms that generate such alterations are still controversial. Seven independent pharmacological approaches were performed in mice to identify the possible mechanisms underlying the decrease of neutrophil activity induced by MDMA and the possible effects of MDMA on host resistance to Listeria monocytogenes. Our data showed that MDMA (10 mg kg(-1)) administration decreases NF kappa B expression in circulating neutrophils. Metyrapone or RU-486 administration prior to MDMA treatment abrogated MDMA effects on neutrophil activity and NF kappa B expression, while 6-OHDA or ICI-118,551 administration did not. As MDMA treatment increased the plasmatic levels of adrenaline and noradrenaline, propranolol pre-treatment effects were also evaluated. Propranolol suppressed both MDMA-induced increase in corticosterone serum levels and its effects on neutrophil activity. In a L. monocytogenes experimental infection context, we showed that MDMA: induced myelosuppression by decreasing granulocyte-macrophage hematopoietic progenitors (CFU-GM) in the bone marrow but increased CFU-GM in the spleen; decreased circulating leukocytes and bone marrow cellularity and increased spleen cellularity; decreased pro-inflammatory cytokine (IL-12p70, TNF, IFN-gamma, IL-6) and chemokine (MCP-1) production 24 h after the infection; increased the production of pro-inflammatory cytokines and chemokines 72 h after infection and decreased IL-10 levels at all time points analyzed. It was proposed that MDMA immunosuppressive effects on neutrophil activity and host resistance to L monocytogenes rely on NF kappa B signaling, being mediated by HPA axis activity and corticosterone. (AU)

• Processo FAPESP: 11/15115-2 - Caracterização das ações do extrato da inflorescência da Achyrocline satureoides sobre a função de neutrófilos na inflamação
• Beneficiário: Eric Diego Barioni
• Linha de fomento: Bolsas no Brasil - Mestrado
• Processo FAPESP: 07/57614-0 - Avaliação dos mecanismos neuroimunes envolvidos na diminuição da atividade de neutrófilos induzida por n-metil-3,4 metilenodioximetanfetamina (MDMA - ecstasy)
• Beneficiário: Viviane Ferraz de Paula
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 09/51886-3 - Neuroimunomodulação: fármacos, estresse e citocinas nas relações entre os sistemas nervoso, endócrino e imune
• Beneficiário: João Palermo Neto
• Linha de fomento: Auxílio à Pesquisa - Temático